liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Small non-coding RNA in early fly development: plasticity, interactions and improved bioinformatic tools
Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

At fertilization, the male and female pronuclei undergo a transformation from germline to pluripotency as they fuse, marking the beginning of Drosophila embryogenesis. As the parental contributions decrease, the zygote takes control of its genome in a process called the maternal-to-zygotic transition (MZT). Several small non-coding RNAs (sncRNAs), a very large and diverse group of RNAs, have regulatory roles during this transition. This includes for example microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs). Regulation by miRNAs mainly occurs through mediating maternal mRNA degradation, while piRNAs operate by repressing transposable elements (TEs) and regulating the nanos-induced embryonic body axis determination.

In this thesis, the complex and dynamic field of early Drosophila embryogenesis and sncRNAs are put in relation to the included papers. In Paper I, I explored the most stress-sensitive embryonic period and found that stress before the midblastula transition retains maternal miRNAs. These miRNAs impact zygotic gene activation by modulating the boundary factor Elba1, leading to compromised transcription control. Paper III examines the piRNA population during MZT. I find differences of unique piRNA sequences in embryos of different ages but not in target preferences, potentially highlighting the importance of constant repression of certain TEs. Paper II addresses specific difficulties with sncRNA seq data analysis and presents a bioinformatic framework to improve these analyses using a sequence-based strategy.

This thesis highlights the intricate interplay of sncRNAs in the critical period of early Drosophila embryogenesis and offers insights into their regulatory roles.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2023. , p. 59
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1873
Keywords [en]
Drosophila, Maternal-to-zygotic transition, sncRNA, miRNA, piRNA, Embryogenesis, Zygotic gene activation
National Category
Bioinformatics and Systems Biology
Identifiers
URN: urn:nbn:se:liu:diva-198696DOI: 10.3384/9789180753395ISBN: 9789180753388 (print)ISBN: 9789180753395 (electronic)OAI: oai:DiVA.org:liu-198696DiVA, id: diva2:1806675
Public defence
2023-11-30, Berzeliussalen, Building 463, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2023-10-23 Created: 2023-10-23 Last updated: 2023-10-23Bibliographically approved
List of papers
1. Stress-sensitive dynamics of miRNAs and Elba1 in Drosophila embryogenesis
Open this publication in new window or tab >>Stress-sensitive dynamics of miRNAs and Elba1 in Drosophila embryogenesis
Show others...
2023 (English)In: Molecular Systems Biology, ISSN 1744-4292, E-ISSN 1744-4292, Vol. 19, no 5, article id e11148Article in journal (Refereed) Published
Abstract [en]

Early-life stress can result in life-long effects that impact adult health and disease risk, but little is known about how such programming is established and maintained. Here, we show that such epigenetic memories can be initiated in the Drosophila embryo before the major wave of zygotic transcription, and higher-order chromatin structures are established. An early short heat shock results in elevated levels of maternal miRNA and reduced levels of a subgroup of zygotic genes in stage 5 embryos. Using a Dicer-1 mutant, we show that the stress-induced decrease in one of these genes, the insulator-binding factor Elba1, is dependent on functional miRNA biogenesis. Reduction in Elba1 correlates with the upregulation of early developmental genes and promotes a sustained weakening of heterochromatin in the adult fly as indicated by an increased expression of the PEV w(m4h) reporter. We propose that maternal miRNAs, retained in response to an early embryonic heat shock, shape the subsequent de novo heterochromatin establishment that occurs during early development via direct or indirect regulation of some of the earliest expressed genes, including Elba1.

Place, publisher, year, edition, pages
WILEY, 2023
Keywords
Drosophila; Elba1; Embryogenesis; miRNA; MZT
National Category
Medical Genetics
Identifiers
urn:nbn:se:liu:diva-193008 (URN)10.15252/msb.202211148 (DOI)000953295100001 ()36938679 (PubMedID)
Note

Funding Agencies|Swedish VR,; Ragnar Soederbergs foundation; Knut Wallenberg foundation

Available from: 2023-04-13 Created: 2023-04-13 Last updated: 2024-01-08
2. Seqpac: a framework for sRNA-seq analysis in R using sequence-based counts
Open this publication in new window or tab >>Seqpac: a framework for sRNA-seq analysis in R using sequence-based counts
Show others...
2023 (English)In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 39, no 4, article id btad144Article in journal (Refereed) Published
Abstract [en]

Motivation: Feature-based counting is commonly used in RNA-sequencing (RNA-seq) analyses. Here, sequences must align to target features (like genes or non-coding RNAs) and related sequences with different compositions are counted into the same feature. Consequently, sequence integrity is lost, making results less traceable against raw data.Small RNA (sRNA) often maps to multiple features and shows an incredible diversity in form and function. Therefore, applying feature-based strategies may increase the risk of misinterpretation. We present a strategy for sRNA-seq analysis that preserves the integrity of the raw sequence making the data lineage fully traceable. We have consolidated this strategy into Seqpac: An R package that makes a complete sRNA analysis available on multiple platforms. Using published biological data, we show that Seqpac reveals hidden bias and adds new insights to studies that were previously analyzed using feature-based counting.We have identified limitations in the concurrent analysis of RNA-seq data. We call it the traceability dilemma in alignment-based sequencing strategies. By building a flexible framework that preserves the integrity of the read sequence throughout the analysis, we demonstrate better interpretability in sRNA-seq experiments, which are particularly vulnerable to this problem. Applying similar strategies to other transcriptomic workflows may aid in resolving the replication crisis experienced by many fields that depend on transcriptome analyses.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2023
National Category
Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:liu:diva-193708 (URN)10.1093/bioinformatics/btad144 (DOI)000968866900001 ()36944267 (PubMedID)
Note

Funding Agencies|Swedish Research Council [2015-03141]; Knut and Alice Wallenberg Foundation [2015.0165]; Ragnar Soderberg; Swedish Research Council for Sustainable Development [2020-01042]

Available from: 2023-05-15 Created: 2023-05-15 Last updated: 2023-10-23

Open Access in DiVA

fulltext(4873 kB)120 downloads
File information
File name FULLTEXT01.pdfFile size 4873 kBChecksum SHA-512
4f7d813adb0b6ac3b9a09509a29a0ff49dde4cb5c397995e1185056810eae69c13aaab599f3cb5afa6ca0af6b4a28cf2f6797d2d384a325bb6daf9f61bcaf5ee
Type fulltextMimetype application/pdf
Order online >>

Other links

Publisher's full text

Authority records

Örkenby, Lovisa

Search in DiVA

By author/editor
Örkenby, Lovisa
By organisation
Division of Cell BiologyFaculty of Medicine and Health Sciences
Bioinformatics and Systems Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 120 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
isbn
urn-nbn

Altmetric score

doi
isbn
urn-nbn
Total: 649 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf